Fibroblast growth factor-23 (FGF-23) is a novel circulating peptide that regulates phosphorus (Pi) and vitamin D metabolism, but the mechanisms by which circulating FGF-23 itself is regulated are unknown. To determine whether the serum FGF-23 concentration is regulated by dietary intake of Pi, we fed wild-type (WT), Npt2a gene-ablated (Npt2a(-/-)), and Hyp mice diets containing varying Pi contents (0.02-1.65%). In WT mice, increases in dietary Pi intake from 0.02-1.65% induced a 7-fold increase in serum FGF-23 and a 3-fold increase in serum Pi concentrations. Across the range of dietary Pi, serum FGF-23 concentrations varied directly with serum Pi concentrations (r(2) = 0.72; P < 0.001). In Npt2a(-/-) mice, serum FGF-23 concentrations were significantly lower than in WT mice, and these differences could be accounted for by the lower serum Pi levels in Npt2a(-/-) mice. The serum concentrations of FGF-23 in Hyp mice were 5- to 25-fold higher than values in WT mice, and the values varied with dietary Pi intake. Fgf-23 mRNA abundance in calvaria was significantly higher in Hyp mice than in WT mice on the 1% Pi diet; in both groups of mice, fgf-23 mRNA abundance in calvarial bone was suppressed by 85% on the low (0.02%) Pi diet. In WT mice fed the low (0.02%) Pi diet, renal mitochondrial 1alpha-hydroxylase activity and renal 1alpha-hydroxylase (P450c1alpha) mRNA abundance were significantly higher than in mice fed the higher Pi diets and varied inversely with serum FGF-23 concentrations (r(2) = 0.86 and r(2) = 0.64; P < 0.001, respectively). The present data demonstrate that dietary Pi regulates the serum FGF-23 concentration in mice, and such regulation is independent of phex function. The data suggest that genotype-dependent and dietary Pi-induced changes in the serum FGF-23 concentration reflect changes in fgf-23 gene expression in bone.
X-linked hypophosphatemic (Hyp) mice exhibit hypophosphatemia, impaired renal phosphate reabsorption, defective skeletal mineralization, and disordered regulation of vitamin D metabolism: In Hyp mice, restriction of dietary phosphorus induces a decrease in serum concentration of 1,25-dihydroxyvitamin D and renal activity of 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase), and induces an increase in renal activity of 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase). In contrast, in wild-type mice, phosphorus restriction stimulates renal 1alpha-hydroxylase gene expression and suppresses that of 24-hydroxylase. To determine the molecular basis for the disordered regulation of vitamin D metabolism in Hyp mice, we determined renal mitochondrial 1alpha-hydroxylase activity and the renal abundance of p450c1alpha and p450c24 mRNA in wild-type and Hyp mice fed either control, low-, or high-phosphorus diets for 5 d. In wild-type mice, phosphorus restriction increased 1alpha-hydroxylase activity and p450c1alpha mRNA expression by 6-fold and 3-fold, respectively, whereas in the Hyp strain the same diet induced changes of similar magnitude but opposite in direction. Phosphorus supplementation was without effect in wild-type mice, whereas in Hyp mice the same diet induced 3-fold and 2-fold increases, respectively, in enzyme activity and p450c1alpha mRNA abundance. In wild-type mice, both renal 1alpha-hydroxylase activity and p450c1alpha mRNA abundance varied inversely and significantly with serum phosphorus concentrations, whereas in Hyp mice the relationship between both renal parameters and serum phosphorus concentration was direct. In Hyp mice, phosphorus restriction induced a significant increase in renal p450c24 mRNA abundance, in contrast to the lack of effect observed in wild-type mice. The present findings demonstrate that regulation of both the p450c1alpha and p45024 genes by phosphorus is disordered in Hyp mice at the level of renal 1alpha-hydroxylase activity and renal p450c1alpha and p450c24 mRNA expression.
Atherosclerotic lesion of coronary artery frequently accompanies intimal hyperplasia of radial artery. We have reported that the lesion of radial artery (intimal hyperplasia) in hemodialysis (HD) patients is associated with early access failure (EAF) as well as ischemic heart disease (IHD) (Am J Kidney Dis. 2003; 41: 422-428). Objective: This study was designed to determine the impact of IHD on the EAF in nondiabetic HD patients. Methods: This study enrolled 125 nondiabetic HD patients who received radiocephalic arteriovenous fistula operation for the first time. We evaluated IHD before the operation through clinical symptoms and electrocardiography and then investigated EAF within 1 year after the operation. We analyzed the access patency rates between the patients with and without IHD, using Kaplan-Meier method and log-rank test. Multiple regression analysis was performed to identify independent risk factors of the EAF. Results: The mean age of the patients was 48 AE 14 years, and the number of females was 54 (43.2%). Of the total 125 patients, 19 patients (15.4%) had IHD before the operation. The EAF developed in 23 patients (18.4%) within 1 years after the operation. The access patency rate in the patients with IHD was lower than that in the patients without IHD (39.7 vs. 88.3%, p < 0.001). IHD and old age were independent risk factors of the EAF in nondiabetic HD patients. But sex, smoking history, hypertension, and the levels of hemoglobin, serum creatinine, albumin, and total cholesterol checked before the operation were not associated with the EAF. Conclusion: This study suggests that IHD is closely associated with EAF in nondiabetic HD patients. Dialysis Staff Time and SupplyCost for the LifeSite System vs. Hemodialysis Catheters D. Shore, S. Vega. West Palm Dialysis --Preferred Medical Group, West Palm Beach, FL, U.S.A.The LifeSite System is a new subcutaneous vascular access option for hemodialysis patients. As the procedure for accessing the Life-Site differs from hemodialysis catheters, we prospectively studied the differences in time required to initiate and discontinue treatments for LifeSite patients compared to patients with hemodialysis catheters. We also collected data on the cost of supplies and the number of alarms during dialysis for both groups. 5 LifeSite and 5 catheter patients were chosen at random for participation in the study. The time required for the ON and OFF procedures was recorded for 3 consecutive dialysis sessions for each patient for a total of 15 observations/group. The average staff time required per session for supply preparation, ON/OFF procedure, dressing changes, and responding to alarms was 15.9 min for the LifeSite and 16.9 min for catheters. Catheter patients experienced 4.5Background: Hemodialysis is often complicated by cardiovascular instability (CVI). We studied factors contributing to
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